Hemicellulose-based nanoaggregate-incorporated biocompatible hydrogels with enhanced mechanical properties and sustained controlled curcumin release behaviors

Local drug delivery has generated considerable interest due to its controlled and sustained drug release at the target site on demand. Nanoaggregate-incorporated composite hydrogels are desirable as local drug delivery systems; however, it is difficult to achieve sustained and controlled hydrophobic drug release and superior mechanical properties in one system. Herein, a "smart" composite hydrogel was synthesized by incorporating hemicellulose-based nanoaggregates into a double network consisting of alginate/Ca2+ and polyacrylic acid-codimethylaminoethyl methacrylate [P(AA-co-DMAEMA)]. Hemicellulose-based nanoaggregates were assembled from xylan-rich hemicellulose laurate methacrylate (XH-LA-MA) polymers and entrapped into the hydrogel framework via chemical fixation. Another composite hydrogel with physically embedded hemicellulose laurate (XH-LA) nanoaggregates was prepared as a comparison. Accordingly, covalently cross-linked XH-LA-MA nanoaggregates in hydrogels resulted in a denser pore structure and reinforced mechanical properties. Nanoaggregate diffusion analysis revealed that covalent bonding between the nanoaggregates and the hydrogel framework contributed to prolonged diffusion behavior. Curcumin (Cur)-loaded XH-LA-MA composite hydrogels enabled sustained Cur release in simulated body fluid and showed stimulus responsiveness toward ethylenediaminetetraacetic acid (EDTA) and/or glutathione (GSH). All the composite hydrogels were biocompatible, as verified by Cell Counting Kit-8 (CCK-8) assay against NIH/3T3 cells. These composite hydrogels hold great potential as a promising dosage form for biomedical applications.